1158
J. Org. Chem. 1992,57, 1158-1161
Supplementary Material Available: Proton NMR spectra for 19b and 25; carbon NMR spectra for 19b and 21; full details on X-ray crystallographicanalyses for compounds 9a, 24, and 25 including tables of coordinates, anisotropic temperature factors,
distances, and angles (27 pages). This material is contained in many libraries on microfiche, immediately follows thia article in the microfilm version of the journal and can be ordered from the ACS; see any current masthead page for ordering information.
Diastereoselection in the Lewis Acid Catalyzed Cycloaddition Reaction of a-Alkoxy Imines' M. Mark Midland* and Roger W. Koops Department of Chemistry, University of California, Riverside, Riverside, California 92521
Received August 27, 1991 The Lewis acid catalyzed cycloaddition reactions of a-benzyloxy imines (RCH(OCH2C6H6)CH=NCH2C6H6) were investigated using 1,3-dimethoxy-l-[(trimethylsilyl)oxy]-1,3-butadiene.The observed diastereoselectivity was dependent on both the Lewis acid and substrate structure. Strong Lewis acids such as diethylaluminum chloride (DEAC) exhibited moderate to good success in promoting the cycloaddition reaction. When DEAC was used as the Lewis acid, the diastereoselectivitywas also dependent on the stoichiometry of the Lewis acid to the substrate. In general, the diastereoselectivity increased with increasing steric bulk of the R group.
Introduction Scheme I The use of heteroatom dienophiles in the Diels-Alder reaction has received much attention in recent years., We have been interested in the cycloaddition reactions of a-heterosubstituted dienophiles such as a-alkoxy aldehydes: a-amino aldehydes: and a-alkoxy ketone^.^ The R$H use of imines as dienophiles has also been of interest, and results using an a,@-dialkoxyimine have been reporteda6 OBn OBn OBn Cycloaddition reactions of imine and iminium species 14 Izl are of use in the construction of complex natural products R= n-pentyl% 9. and thus this reaction has received considerable attention., [-propyl ab sb t-butyl IC sc Grieco has described cycloaddition reactions of iminium ion species generated under Mannich-type c~nditions.~ Scheme I1 Danishefsky has reported the Lewis acid catalyzed cycloOTMS addition of simple alkyl imines in the synthesis of the natural product ipaldibine.8 Ojima has observed reactions LA of imines with silyl ketene acetals catalyzed by titanium OMe OMe MeO tetrachloride (TiClJ.9 Ojima provided evidence suggeating 1 (threo) (erythro) that the reaction proceeds by an addition-cyclization R= n-pentyl(. sa pathway rather than a cycloaddition pathway. Kunz has w [-propyl 4b sc t-butyl4~ reported the Lewis acid mediated cycloaddition reaction of imines derived from pivaloylated sugars.'O Kunz rainvolving imine cycloadditions." The endo/exo approach tionalized a "chelation-controlled"mechanism based upon of the dienophile was influenced by the group on the imine the observed diastereoselectivities. The role of the group nitrogen. The selectivity of these reactions was also deon the imine nitrogen has been the focus of recent work pendent on whether kinetic or thermodynamic control was employed. (1) Taken in part from the Ph.D. Dissertation of R.W.K., University In our own laboratories, we have investigated the cyof California, Riverside, 1990. cloaddition reactions of simple aldimines with an activated (2) For reviews, see: Weinreb, S. M. Chem. Rev. 1989, 89, 1234. diene 1,3-dimethoxy-1-[(trimethylsily1)oxyl-1,&butadiene Weinreb, S. M.; Boger, D. L. Hetero Diels-Alder Methodology in Organic Synthesis; Academic Press: New York, 1987. Weinreb, S. M.; Staib, R. (Brassard'sdiene,', l).I3 The reaction proceeds efficiently R. Tetrahedron 1982,38,3087. when a strong Lewis acid such as diethylaluminum chloride (3) (a) Midland, M. M.; Koops, R. W. J . Org. Chem. 1990,55, 5058. @ M C ) or Tic&is used. Boron trifluoride and magneaium (b) Midland, M. M.; Graham, R. S. J.Am. Chem. SOC.1984,106,4294. See also: (c) Danishefsky, S.;Pearson, W. H.; Harvey, D. F.; Maring, C. dibromide (MgBr,) were also efficient catalysts. PrelimJ.; Springer, J . P. J. Am. Chem. SOC.1986, 107, 1256 and references inary results also indicated that the choice of Lewis acid therein. (d) Sims, J. J.; Castellino, S. Tetrahedron Lett. 1984,25,2307. was important in the stereochemical outcome of cyclo(4) (a) Midland, M. M.; Afonso, M. M. J. Am. Chem. SOC.1989,111, 4368. (b) J u r d , J.; Golebioewki, A. Chem. Rev. 1989,89,149. Jurczak, additions involving a,@-dialkoxyimines. J . J. Org. Chem. 1989,54, 2496. Stereochemical results of cycloadditions using a variety ( 5 ) Midland, M. M.; Koops, R. W.; Carter, D. S., manuscript in prepof a-alkoxy imines and diene 1 are reported within. The aration. (6) Midland, M. M.; McLoughlin, J. I. Tetrahedron Lett. 1988, 29, nature of the Lewis acid in promoting the cycloaddition +
4653. (7) Grieco, P. A.; Larsen, S. D. J . Org. Chem. 1986,51,3553. Grieco, P. A.; Lareen, S. D. J. Am. Chem. SOC.1986,107, 1768. (8) Daniehefsky, S.; Vogel, C. J. Org. Chem. 1986,51, 3915. (9) Ojima, I.; Brandstadter, 5.M. Tetrahedron Lett. 1987,28, 1067. (10) Kunz, H.; Pfrengle, W. J. Org. Chem. 1989,54, 4261. Kunz, H.; Pfrengle, W. Angew. Chem., Int. Ed. Engl. 1989, 28, 1067.
RgH
(11) Wartaki, L.; Seyden-Penne,J.; Veyrat-Martin, C.; Le Cuz, L.; Bob, C.; Philoche-Levisalles, M. J. Org. Chem. 1990,55,4870. (12) Brassard, P.; Savard, J . Tetrahedron Lett. 1979,20, 4911. (!3) McLoughlin, J. I. Ph.D. Thesis Dissertation, University of California, Riverside, 1986.
0022-326319211957-1158$03.00/00 1992 American Chemical Society
Cycloaddition Reaction of a-Alkoxy Imines
J. Org. Chem., Vol. 57, No. 4, 1992 1159
Table I. Cycloaddition Results of a-Alkoxy Imines with Diene 1 ~~
imine
3a 3b 3c 38
3a 3b 3b 3c 3c
Lewis acid
SnCl. SnC1; SnC1, EhAlCl' EhAlCl8 EhAlC1' EhAlCl8 EhAICle EhAlClg
threo:erythro 83:17 91:9 >99ld 5050 m10 4060 6040 91:9 >99ld
Scheme 111' 0
0
4c
6
yield," % 15'
20c
r n
7
10c 60' 55r 66 58r 68r 75r
1
7
" (a) Na/NH3; (b) carbonyldiimidazole/THF.
*
Isolated yield of lactam(s). 1.1 equiv of Lewis acid. Large portion of starting aldehyde recovered. Only one diastereomer observed by capillary GC. e0.9 equiv of Lewis acid. fSmall amount (90% as estimated by proton and carbon NMR. General Procedure for the Cycloaddition Reaction with DEAC Catalysis. A solution of imines 3a-c as described above (typical scale 0.5-1.0 mmol) was cooled under argon to -78 "C. Diethylaluminum chloride (0.9 or 2.1 equiv) was added slowly via syringe. After a 5-min equilibration, diene 1 (1.2-1.5 equiv) was added slowly (5-10 min). After 4 h, the red solution was warmed to -23 "C and stirred for 4-6 h. The solution was warmed to rt for 12 h. The reaction was quenched at 0 "C by careful addition of an equal volume of methanol. The solution was warmed to room temperature and diluted with diethyl ether (2X volume). An equal volume of water was added and the layers were separated. The aqueous layer was extracted with diethyl ether (2x1, and the combined ether layers were dried (MgSOJ, filtered, and concentrated to yield the crude lactam as an oil. The crude lactam was purified via flash chromatography (ethyl acetate/hexanes, 1:l). The mixture of diastereomers was analyzed by capillary GC. Each diastereomer was isolated via preparative HPLC. Lactam 4a: mass calculated for C&ISrNO3(M 1) 408.25387, maw found (Cl, M + l),408.2520; MS (Cl) 408.21691; 'H NMR (CDC13) 6 3.62 (dt, J = 6.83,7.81 Hz,l-H, Hi), 3.40 (dd, J = 7.32, 7.81 Hz, l-H, H6); 13C NMR (CDClJ 6 167.5, 138.1, 138.4,128.6, 128.3, 127.8, 127.8, 127.7, 127.3, 93.4, 79.2, 72.9, 67.4, 55.5, 55.7, 48.3, 31.9,28.6,25.2,22.7,14.1;IR (NaC1, cm-') 3050,2950,1650, 1610,1450,1380,1230. Capillary GC indicated a purity of 100% (250 "C for 2 min, 10 OC/min to 275 OC for 20 mh, retention time was 16.9 min). Lactam 5a: exact mass same as 4a; 'H NMR (CDC13)S 3.60 (m, l-H, Hi,), 3.40 (ddd, J = 1.95,7.32,5.70 Hz,l-H, '3C NMR (CDCld 6 167.5,138.4,128.8, 128.6,128.3,127.8, 127.7,127.3,93.4, 79.2,72.9,67.4,55.7,55.2,48.3,31.9,28.6,25.2,22.7,14.1. Capillary GC indicated a purity of 100% (conditions as described for 48, retention time was 17.5 min). Lactam 4 b mass calculated for CNH3DNO3(M + 1) 380.2226, mass found (Cl, M 1) 380.2201; MS (Cl) 380.21691; 'H NMR (CDC13) 6 3.52 (dd, J = 1.90, 6.83 Hz, 1-H, Hi,), 3.40 (ddd, J = 1.0,4.9,6.83Hz, l-H, I&); '3C NMR (CDCld 6 166.7, 138.8,138.4, 128.6, 128.2, 127.8, 127.3, 92.9, 84.6, 75.4, 55.3, 54.2, 47.7, 28.3, 20.3,17.7;IR (NaC1, cm-')3050,2975,1630,1610,1450,1380,1220. Capillary GC indicated a purity of 99% (conditions as described for 4a, retention time was 12.2 min). Lactam 5 b exact mass same as 4b; 'H NMR (CDC13)6 3.44 (m, 2 H); '3c NMR (CDCld 6 166.0,138.4,138.3,128.2,128.0,127.8, 127.5, 127.0, 94.0, 83.4, 75.2, 55.6, 54.6, 49.5, 30.3, 20.6, 15.0. Capillary GC indicated a purity of 100% (conditions as described for 4a, retention time was 12.8 min). Lactam 4c: mass calculated for C&,,N03 (M + 1) 394.2382, mass found (Cl, M 1) 394.2406; MS (Cl) 394.21691; 'H NMR (CDC13) 6 3.49 (dd, J = 6.8,8.3Hz, l-H, Hs), 3.15 (d, J = 8.3 Hz, l-H, Hit); 13C NMR (CDClJ 6 166.5, 138.8, 138.1, 128.4, 128.2, 127.6, 127.5,126.9,94.4,86.3,75.3,55.7,52.5,49.1,35.9,33.5,26.2; IR (NaC1, c") 3050,2950,1640,1620,1425,1380,1210. CapiUary GC indicated a purity of 100% (conditions as described for 4a, retention time was 13.2 min). Lactam 5c: exact mass same as 4c; 'H NMR (CDC13)6 3.56 (dd, J = 1.45,8.3 Hz,1-H, 3.33 (8, l-H, Hi,); '3C N M R (CDCld 6 166.2, 138.8,138.1, 128.2, 128.0, 127.6, 127.4, 127.0, 93.1,86.0, 75.0, 56.2, 53.4, 49.1, 36.0, 33.5, 26.2. Capillary GC indicated a purity of 100% (conditions as described for 4a,retention ime was 13.6 min). Cycloaddition Reactions with Tin Tetrachloride Catalyst. The solution of imine (typical scale was 0.5 mmol) was cooled under argon to -78 OC, and SnCl, (1.1 equiv) was added. The red solution was equilibrated for 5 min, and 1 (1.2-1.5 equiv) was added slowly. A gel typically formed, the flask was warmed to -23 "C (homogeneous), and the solution was stirred for 4-8 h.
+
m;
+
+
w,
J. Org. Chem. 1992,57,1161-1169 The solution was warmed to room temperature over 12-16 h. Quench and workup were identical to that described above for DEAC. Deprotection of Lactam 4c: Formation of 6. Lactam 4c (0.100 g, 0.30 mol)was dissolved in 20 mL of liquid ammonia. Sodium metal (0.069 g, 3.0 mmo1,lO equiv) was added, and a deep blue color was obtained. The solution was allowed to reflux for 1h with the persistence of blue color. The reaction was quenched with ammonium chloride (0.200 g, 13 equiv) and allowed to warm to room temperature in a hood. The residue was triturated with acetonitrile (5 mL), and the decanted solution was concentrated to a residue. The residue was triturated with methanol (5 mL) and was filtered through cotton. The filtrate was concentrated to yield an oil. The oil was purified by column chromatography (silica gel, CHC13/MeOH, 9/1) to yield 0.030 g of semisolid (57% yield). Purity was >90% as established by TLC: 'H NMR (CDC13)6 6.20 (bs,1-H),3.79 (m, 2-H), 3.35 (s,3-H), 3.12 (bs,1-H), 2.54 (t, 1-H),2.46 (d, J = 4.1 Hz, 1-H), 2.06 (at,J = 1.0, 13.5 Hz, 1-H), 1.74 (ddd, J = 2.4, 11.1, 13.5 Hz, 1-H), 0.996 (8, 9-H). Preparation of 7. Deprotected compound 6 (0.030 g, 0.14 mmol) was dissolved in anhydrous THF (1 mL). 1,l'Carbonyldiimidazole (0.024 g, 0.14 mmol) was added, and the solution was warmed to 35-40 "C for 24 h. The solution was concentrated in vacuo, and the crude oil was purified by column chromatography (silica gel 230 m, CHC13/MeOH, 9/1). The desired fractions were combined and concentrated to yield 15 mg of oil (50% yield). Purity was >90% as determined by TLC exact mass calculated for C12H20N04(M + l ) , 242.13923, exact mass found (Cl, M + 11, 242.1400; MS (Cl) 242.210128; 'H NMR
1161
(CDCl3) 6 4.25 (ddd, J = 3.00, 9.40, 11.1 Hz, 1-H), 3.90 (d, J = 9.40 Hz, 1-H), 3.85 (m, J = 3.00,3.30,5.10 Hz, 1-H),3.36 (s,3-H), 2.75 (dd, J = 3.00, 5.10 Hz, 2-H), 2.30 (ddd, J = 3.00,3.30, 13.8 Hz, 1-H), 1.75 (ddd, J = 3.30,11.1, 13.8 Hz, 1-HI, 1.03 (8,9-H); 13CNMR (CDCl3) 6 166.6,150.9,87.3,72.5,56.3,51.7,38.6,33.8, 33.3, 25.1. Nuclear Overhauser Effect (NOE) Spectroscopy. Homonuclear decoupling was first performed (QE 300 NMR spectrometer) to identify irradiation frequencies. The irradiation power was 2900, and the offset was determined from chloroform at 7.26 ppm. Irradiation and pulse length were 20 s followed by a 0.5-8delay. The spectrum was obtained after 24 pulses. The NOE experiment was performed with irradiation power of 3200 under identical pulse conditions. The reference spectrum was obtained with a 10000-Hz offset.
Acknowledgment. Financial support of the University of California, Riverside, Committee on Research is gratefully acknowledged. Registry No. I, 74272-66-5; 2a, 96759-99-8; 2b, 96925-01-8; 2c, 128495-75-0;3a,137869-45-5;3b, 137869-46-6; 3c, 137869-47-7; 4a,137869-48-8;4b, 137869-49-9;4c, 137869-50-2;5a, 13789523-9; 5b, 137869-51-3;5c, 137869-52-4;6,137869-53-5;7,137895-24-0; SnC14,7646-78-8; PhCH2NH2,100-46-9; diethylaluminum chloride, 96-10-6. Supplementary Material Available: Spectral data for compounds 3a-q 4a-c, 5a-q and 7 (16 pages). Ordering information is given on any current masthead page.
Tunable Regioselectivity Associated with the Reaction of 2,3-Dihalo-1-(phenylsulfony1)-1-propenes with Ambident Nucleophilic Reagents Albert Padwa,* David J. Austin, Masaru Ishida,' Cheryl L. Muller,$ S. Shaun Murphree, and Philip E. Yeske Department of Chemistry, Emory University, Atlanta, Georgia 30322 Received September 10,1991
2,3-Dihalo-1-(phenylsulfonyl)-l-propenes, obtained by the addition of bromine or iodine onto (phenylsulfonyl)propadiene,were found to exhibit interesting reactivity as both mono- and dielectrophiles, with the mode of reactivity depending upon the nature of the nucleophile as well as the reaction conditions. Thus, amines or thiophenols smoothly effected substitution at the allylic site, while sodium methoxide reacted at the vinylic position through an addition-elimination process. In the realm of ambident nucleophiles, 8-dicarbonyl compounds in produced by initial a medium of NaHltert-butoxide/THF gave 2-alkyl-3-acyl-4-[(phenylsulfonyl)methyl]fura11~, allylic S Ndisplacement ~ followed by 5exo-trig cyclization. Conversely, such &dicarbonyla in a methoxide/methanol system yielded 2-alkyl-4-[(phenylsulfonyl)methyl]furans,where reaction proceeds by initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of silver tetrafluoroborate resulted in products derived from SN2displacement at the allylic site. Thioamides could be used to form 2-substituted thiazoles by initial allylic displacement by the sulfur atom followed by an addition-elimination reaction. Thus, by the proper choice of a variety of compounds were prepared from 2,3-dihalo-l-(phenylsulfonyl)-l-propenes reagents and reaction conditions.
Allenes play an important role in many aspects of organic Their ability to enter into reactions as either a nucleophile or an electrophile provides the synthetic chemist with a variety of meihods for preparing more complex compounds.' T h e addition of electrophilic reagents to allenes is a well-studied process,6 as is the synthesis of alkene-substituted heterocycles via intramo+Currentaddress: Department of Chemistry, Faculty of Engineering, Gifu University Yanagido, Gifu 501-11, Japan. C.L.M.is pleased to acknowledge the NIH for a postdoctoral fellowship (CA-08845-01).
*
0022-3263/92/1957-1161$03.00/0
lecular nucleometallationsof allenes using mercury(I1) or salt^.^ For simple alkyl-substituted allenes,
silver(1)
(1) The Chemistry of Allenes; Landor, S. R., Ed.; Academic Press: London, 1982; vols.1-111. (2) Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis; Wiley-Inter5cience: New l984. (3) Blake, P. In The Chemistry of Ketenes, Allenes and Related Compounds; Wiley-Interscience: New York, 1980; p 344. (4) Caserio, M. C. In Selective Organic "'ransformatiom;Thyagarajan, B. s.;Ed,; ~ i l ~ ~N~~- Yo&, ~ 1970; ~ 239. ~ ~ ~ ~ i (5) Smadja, W. Chem. Reu. 1983,83,263. (6) Walkup, R. D.; Park, G. Tetrahedron Lett. 1987,28, 1023. (7) Gelin, R.; Gelin, S.; Albrand, M. Bull. SOC. Chim. Fr. 1972,1946.
0 1992 American Chemical Society
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~
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